Lifeboat Foundation

Bioengineers and life scientists incorporate hybridoma technology to produce large numbers of identical antibodies, and develop new antibody therapeutics and diagnostics. Recent preclinical and clinical studies on the technology highlight the importance of antibody isotypes for therapeutic efficacy. In a new study, a research team in Netherlands have developed a versatile Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) and homology directed repair (HDR) platform to rapidly engineer immunoglobin domains and form recombinant hybridomas that secrete designer antibodies of a preferred format, species or isotype. In the study, Johan M. S. van der Schoot and colleagues at the interdisciplinary departments of immunology, proteomics, immunohematology, translational immunology and medical oncology, used the platform to form recombinant hybridomas, chimeras and mutants. The stable antibody products retained their antigen specificity. The research team believes the versatile platform will facilitate mass-scale antibody engineering for the scientific community to empower preclinical antibody research. The work is now published on Science Advances.

Monoclonal antibodies (mAb) have revolutionized the medical field with applications to treat diseases that were once deemed incurable. Hybridoma technology is widely used since 1975 for mAb discovery, screening and production, as immortal cell lines that can produce large quantities of mAbs for new antibody-based therapies. Scientists had generated, validated and facilitated a large number of hybridomas in the past decade for preclinical research, where the mAb format and isotypes were important to understand their performance in preclinical models. Genetically engineered mAbs are typically produced with recombinant technology, where the variable domains should be sequenced, cloned into plasmids and expressed in transient systems. These processes are time-consuming, challenging and expensive, leading to outsourced work at contract research companies, which hamper the process of academic early-stage antibody development and preclinical research.

In its mechanism of action, the constant antibody domains forming the fragment crystallizable – (Fc) domain are central to the therapeutic efficacy of mAbs since they engage with specific Fc receptors (FcRs). Preceding research work had highlighted the central role of Fc in antibody-based therapeutics to emphasize this role. Since its advent, CRISPR and associated protein Cas-9 (CRISPR-Cas9)-targeted genome editing technology has opened multitudes of exciting opportunities for gene therapy, immunotherapy and bioengineering. Researchers had used CRISPR-Cas9 to modulate mAb expression in hybridomas, generate a hybridoma platform and engineer hybridomas to introduce antibody modification. However, a platform for versatile and effective Fc substitution from foreign species within hybridomas with constant domains remains to be genetically engineered.

Ira Pastor, ideaXme longevity and aging ambassador and founder of Bioquark, interviews James Strole, Co-Founder and Co-Director of People Unlimited and Director of the Coalition For Radical Life Extension.

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To most of us, zapping neurons with electricity to artificially “incept” memories, sensation, and movement still sounds crazy. But in some brain labs, that technology is beginning to feel old school. As a new review in Nature Biotechnology concludes: get off the throne, electrodes, there are plenty of other neural probes in town. They dance to the tune of light or chemicals, and in some cases, they’re bilingual.

Here’s a brief tour into the wild west of neural implants. Some require genetic engineering, and because of that have only been proven in experimental animals. But if history is any indication, brain-manipulation technologies don’t tend to stay in the lab. Watch out, you may see some trickling down into potential human use in the next few years.

The human body is an incredible machine. It is impossible to determine which is the essential body part for sustaining life — because there is no single indispensable part. If your heart stops beating, you will die. If your lungs stop working, your brain — and thus all of your cells — will eventually die. Without a stomach or intestines you cannot acquire nutrients and you will die. All parts are critical for optimal function, for sustaining life.

Synthetic biology as a field is no different. There are those that supply DNA — arguably the critical building block for every single synthetic biology application. There are those that automate and scale components of the design-build-test cycle to enable innovation to effect change in meaningful timelines. But when all of those parts come together with a single goal, the power of synthetic biology reaches new levels.

Such potential is exactly what Arzeda — through a collaboration with TeselaGen, Twist Bioscience, and Labcyte — has brought to us. Each company, a giant in its own right, provides an essential, needed component to an elegant, efficient workflow that can best be described as a “DNA assembly line” for more rapid, efficient protein design and production. The companies’ products work seamlessly: Twist produces the DNA fragments needed to make protein-expressing plasmids, Labcyte’s acoustic liquid handler (the Echo 525) facilitates rapid DNA assembly, and TeselaGen’s DNA assembly design and laboratory automation software connects the two, designing plasmids and ordering the necessary sequences from Twist while generating worklists for the Echo to execute.